Modern cancer research indicates that cancers driven by genetic mutations in the same chemical pathway (a group of proteins in a cell that work together) may be more closely related, even if they occur in different parts of the body, than two cancers driven by different mutations that occur in the same organ. Current U.S. Food and Drug Administration (FDA) standards, however, still use the traditional anatomical location-based categories when approving cancer drugs (eg, lung cancer vs pancreatic cancer). As a result, a drug that is approved for treating a specific cancer caused by a given mutation must undergo new clinical trials to get approved for treating a cancer driven by the same mutation in another body part. However, the FDA’s ‘cancer czar’ recently floated an unofficial proposal for approving cancer drugs based on the chemical pathways they target. Such a change could greatly streamline cancer drug development.

Two chemotherapy drugs may be better than one against melanoma, according to results from an ongoing clinical trial that were presented at the 2013 meeting of the International Society for Melanoma Research. The drugs were dacarbazine, which is U.S. Food and Drug Administration (FDA)-approved for melanoma, and paclitaxel, which is FDA-approved for breast, lung, and pancreatic cancers. In a phase III trial of 529 melanoma patients, the drug combination kept tumors from growing two times longer than dacarbazine alone (4.8 vs 2.5 months, respectively). The subgroups that did best included men and people with melanomas that had spread to the liver or brain. This is particularly encouraging for the latter group because they have the worst prognosis.

New clinical trial results suggest that adding the drug nintedanib (Vargatef) to second-line chemotherapy can improve survival for some patients with non-small cell lung cancer (NSCLC). Patients with advanced NSCLC whose cancer had progressed after first-line chemotherapy received either Vargatef and the chemotherapy drug docetaxel (Taxotere) or Taxotere alone. On the whole, Vargatef was associated with slightly longer times without worsening of the cancer (3.4 months vs 2.7 in the Taxotere-only group), but no improvement in overall survival. However, in patients with lung adenocarcinoma, a subtype of NSCLC, the addition of Vargatef improved overall survival by over 2 months (12.6 months vs 10.3 with Taxotere alone). Vargatef disrupts the formation of new blood vessels that feed growing tumors.

Because melanomas can quickly resist BRAF inhibitor drugs alone or in combination with MEK inhibitors, researchers are testing a new combination treatment: the BRAF inhibitor vemurafenib and PX-866, which inhibits a cancer pathway called PI3K. In a phase I/II clinical trial of 19 people with melanomas that have BRAF mutations, the vemurafenib/PX-866 combination shrank tumors in 10 of them. These findings were presented at the 10th International Congress of the Society for Melanoma Research in Philadelphia. However, while results so far are encouraging, it will take larger trials to see if this new combo treatment really overcomes drug resistance in melanomas. This ongoing trial is still accepting new participants.

Two pharmaceutical giants are teaming up on a phase I/II clinical trial to see if their anti-melanoma drugs work better together than on their own. The drugs are GlaxoSmithKline’s Mekinist (trametinib), a U.S. Food and Drug Administration (FDA)-approved MEK inhibitor (a drug that targets MEK proteins), and Pfizer’s palbociclib, an experimental inhibitor of proteins called cyclin dependent kinases. These proteins make cells divide and are abnormally active in many cancers; the FDA has fast-tracked the review of using palbociclib to treat breast cancer. In addition, GlaxoSmithKline is already testing the combination of Mekinist with dabrafenib, the company’s experimental BRAF inhibitor.

Two targeted treatments that are U.S. Food and Drug Administration (FDA)-approved for melanoma may be even more effective together. The drugs are dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor. In a phase II clinical trial with 160 people, the median survival was nearly 2 years with the combination treatment compared to 20 months with dabrafenib alone. These findings were presented at the 10th International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania. Now, the dabrafenib/trametinib combo has advanced to phase III trials.

Blocking a protein that protects tumor cells may shrink melanomas, according to results from an ongoing trial that were presented at the 10th International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania. Called PD-L1, the protein shields tumor cells from the immune system and it can be blocked by a drug called MPDL3280A. The phase I trial included 45 people with melanoma who were treated with the PD-L1 blocker, and tumors shrank in one-third of them. This PD-L1 blocker is also being tested in a phase I trial in combination with the BRAF inhibitor drug vemurafenib, as well as in several phase II trials against renal cell carcinoma and non-small-cell lung cancer (NSCLC). In addition, two drugs similar to this PD-L1 blocker (nivolumab and MK-3475) are being tested in phase III trials against melanoma.

A type of white blood cell can infiltrate and attack tumors, and researchers have just launched a clinical trial of an experimental immunotherapy designed to sharpen this attack against melanoma. These white blood cells are called killer T cells, and the first step is collecting them from people with melanomas that have spread. Then two genes are inserted into the killer T cells to make them seek tumor cells. Next, the people are treated with chemotherapy to wipe out their remaining T cells, which do not recognize tumor cells as abnormal. The final step is treating people with their own genetically-modified killer T cells in hopes that these will then attack tumors. This phase I trial is currently recruiting participants.

An experimental immunotherapy may keep people with melanoma alive for up to 1 year, according to findings presented at the 2013 International Congress of the Society for Melanoma Research in Philadelphia, Pennsylvania. The drug (MK-3475) blocks a protein, called PD-1, that lets cancer cells evade the immune system. Researchers treated 135 people with MK-3475 and found that tumors shrank in 40% and disappeared in 9%. Altogether, this drug is being tested in more than 3,000 people with melanoma or breast, bladder, colorectal, or lung cancer. In addition, another experimental PD-1 blocker called nivolumab is being tested alone and in combination with the U.S. Food and Drug Administration (FDA)-approved Yervoy (ipilimumab) against melanoma and blood, breast, gastric, kidney, liver, lung, and pancreatic cancers.